Effects of mitochondrial dysfunction on the immunological properties of microglia

J Neuroinflammation. 2010 Aug 11;7:45. doi: 10.1186/1742-2094-7-45.

Abstract

Background: Neurodegenerative diseases are characterized by both mitochondrial dysfunction and activation of microglia, the macrophages of the brain. Here, we investigate the effects of mitochondrial dysfunction on the activation profile of microglial cells.

Methods: We incubated primary mouse microglia with the mitochondrial toxins 3-nitropropionic acid (3-NP) or rotenone. These mitochondrial toxins are known to induce neurodegeneration in humans and in experimental animals. We characterized lipopolysaccharide- (LPS-) induced microglial activation and the alternative, interleukin-4- (IL-4-) induced microglial activation in these mitochondrial toxin-treated microglial cells.

Results: We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta), they did inhibit part of the IL-4-induced alternative activation, as measured by arginase activity and expression, induction of insulin-like growth factor 1 (IGF-1) and the counteraction of the LPS induced cytokine release.

Conclusions: Mitochondrial dysfunction in microglial cells inhibits part of the IL-4-induced alternative response. Because this alternative activation is considered to be associated with wound healing and an attenuation of inflammation, mitochondrial dysfunction in microglial cells might contribute to the detrimental effects of neuroinflammation seen in neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Blotting, Western
  • Cell Death / drug effects
  • Cell Death / immunology
  • Cells, Cultured
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Cytokines / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / immunology
  • Insulin-Like Growth Factor I / metabolism
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / immunology*
  • Microglia / metabolism
  • Mitochondria / drug effects
  • Mitochondria / immunology*
  • Mitochondria / metabolism
  • Neurotoxins / pharmacology
  • Nitro Compounds / pharmacology
  • Propionates / pharmacology
  • Rotenone / pharmacology
  • Uncoupling Agents / pharmacology

Substances

  • Cytokines
  • Lipopolysaccharides
  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • Uncoupling Agents
  • Rotenone
  • Insulin-Like Growth Factor I
  • 3-nitropropionic acid